tbuckley/cabot-search huggingface dataset:
Stem-like signatures in human meningioma cells are under the control of CXCL11/CXCL12 chemokine activity
Authors: Federica Barbieri, Adriana Bajetto, Irene Dellacasagrande, Agnese Solari, Roberto Würth, Virginia Fernandez, Silvia Rancati, Davide Ceresa, Irene Appolloni, Giuseppa De Luca, Mariella Dono, Paolo Nozza, Piero Schiapparelli, Monica Gambaro, Pietro Fiaschi, Gabriele Gaggero, Nicolò Costanzo, Stefano Thellung, Paolo Malatesta, Aldo Pagano, Gianluigi Zona, Davide De Pietri Tonelli, Tullio Florio
Journal: Neuro-Oncology (2023)

Abstract Background Meningiomas are mainly benign brain tumors, although about 20% of histologically benign cases are clinically aggressive and recur after resection. We hypothesize that meningioma brain invasiveness and recurrence may be related to the presence of cancer stem cells and their high responsiveness to the CXCL12-CXCR4/CXCR7 chemokine axis. The aim of this study was to isolate meningioma stem cells from human samples, characterize them for biological features related to malignant behavior, and to identify the role of CXCR4/CXCR7 in these processes. Methods Meningioma stem cells were isolated from patient-derived primary cultures in stem cell-permissive conditions, and characterized for phenotype, self-renewal, proliferation and migration rates, vasculogenic mimicry (VM), and in vivo tumorigenesis, in comparison with differentiated meningioma cells and stem-like cells isolated from normal meninges. These cell populations were challenged with CXCL12 and CXCL11 and receptor antagonists to define the chemokine role in stem cell-related functions. Results Stem-like cells isolated from meningioma cultures display higher proliferation and migration rates, and VM, as compared to meningioma non-stem cells or cells isolated from normal meninges and were the only tumorigenic population in vivo. In meningioma cells, these stem-like functions were under the control of the CXCR4/CXCR7 chemokine axis. Conclusions We report a role for CXCL11 and CXCL12 in the control of malignant features in stem-like cells isolated from human meningioma, providing a possible basis for the aggressive clinical behavior observed in subsets of these tumors. CXCR4/CXCR7 antagonists might represent a useful approach for meningioma at high risk of recurrence and malignant progression.
Association of Health Care Utilization and Access to Care With Vascular Assessment Before Major Lower Extremity Amputation Among US Veterans
Authors: Olamide Alabi, Surabhi Beriwal, Julia W. Gallini, Xiangqin Cui, Christine Jasien, Luke Brewster, Kelly J. Hunt, Nader N. Massarweh
Journal: JAMA Surgery (2023)

Patient-level characteristics alone do not account for variation in care among US veterans with peripheral artery disease (PAD). Presently, the extent to which health care utilization and regional practice variation are associated with veterans receiving vascular assessment prior to major lower extremity amputation (LEA) is unknown.
Kidney Function in Patients with Ovarian Cancer Treated with Poly (ADP-ribose) polymerase (PARP) Inhibitors
Authors: Shruti Gupta, Paul E Hanna, Tianqi Ouyang, Karla Sofia Yamada, Rani Sawtell, Qiyu Wang, Nurit Katz-Agranov, Lea Feghali, Carolyn N Krasner, Sara Bouberhan, Cesar M Castro, Meghan E Sise
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking. Methods We identified adults treated with olaparib or niraparib between 2015 and 2021 at a major cancer center in Boston, MA, USA. We determined the incidence of any acute kidney injury (AKI), defined as at least a 1.5-fold rise in serum creatinine from baseline in the first 12 months following PARPi initiation. We calculated the percentage of patients with any AKI and sustained AKI and adjudicated the etiologies by manual chart review. We compared trajectories in estimated glomerular filtration rate (eGFR) among PARPi-treated and carboplatin and paclitaxel-treated patients with ovarian cancer, matched by baseline eGFR. Results Of 269 patients, 60 (22.3%) developed AKI, including 43 of 194 (22.1%) olaparib-treated patients and 17 of 75 (22.7%) niraparib-treated patients. Only 9 of 269 (3.3%) had AKI attributable to the PARPi. Of the 60 patients with AKI, 21 (35%) had sustained AKI, of whom 6 had AKI attributable to the PARPi (2.2% of the whole cohort). eGFR declined within 30 days post-PARPi initiation by 9.61 (SD = 11.017) mL/min per 1.73 m2 but recovered by 8.39 (SD = 14.05) mL/min per 1.73 m2 within 90 days after therapy cessation. There was no difference in eGFR at 12 months post-therapy initiation in patients receiving PARPi or controls receiving carboplatin and paclitaxel (P = .29). Conclusions AKI is common following PARPi initiation as is a transient decline in eGFR; however, sustained AKI directly attributable to the PARPi and long-term eGFR decline are uncommon.
Court Rulings Complicate Decisions for Pregnant Patients
Journal: Cancer Discovery (2023)

Recent legislation restricting or eliminating access to abortion in many states intensifies the challenges faced by pregnant women with cancer, according to experts who spoke during the Presidential Select Symposium: Pregnancy and Cancer at the American Association for Cancer Research Annual Meeting 2023. The emerging legal landscape also presents medical, moral, and ethical dilemmas for physicians when discussing pregnancy termination as an option in high-risk situations.
The emerging role of the small intestinal microbiota in human health and disease
Authors: Renate A. A. A. Ruigrok, Rinse K. Weersma, Arnau Vich Vila
Journal: Gut Microbes (2023)

The human gut microbiota continues to demonstrate its importance in human health and disease, largely owing to the countless number of studies investigating the fecal microbiota. Underrepresented in these studies, however, is the role played by microbial communities found in the small intestine, which, given the essential function of the small intestine in nutrient absorption, host metabolism, and immunity, is likely highly relevant. This review provides an overview of the methods used to study the microbiota composition and dynamics along different sections of the small intestine. Furthermore, it explores the role of the microbiota in facilitating the small intestine in its physiological functions and discusses how disruption of the microbial equilibrium can influence disease development. The evidence suggests that the small intestinal microbiota is an important regulator of human health and its characterization has the potential to greatly advance gut microbiome research and the development of novel disease diagnostics and therapeutics.
How Do We Credit the Evidence Generated From Subgroup Analyses in Randomized Clinical Trials?—Reply
Authors: Mark A. Hlatky, Neil J. Stone, JoAnn E. Manson
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Anatomic Locations of Procedurally Treated Keratinocyte Carcinomas in the US Medicare Population
Authors: Lucy J. Navsaria, Yao Li, Sanjna Tripathy, Madisyn L. Cox, Candice L. Hinkston, David J. Margolis, Mackenzie R. Wehner
Journal: JAMA Dermatology (2023)

Keratinocyte carcinomas are the most common cancers in the US. However, keratinocyte carcinomas are not included in US national cancer registries, and information on the anatomic locations of keratinocyte carcinomas is lacking.
A retrospective study of MYC rearranged diffuse large B-cell lymphoma in the context of the new WHO and ICC classifications
Authors: Dima El-Sharkawi, Amit Sud, Catherine Prodger, Jahanzaib Khwaja, Rohan Shotton, Brian Hanley, Victoria Peacock, Ying Ying Peng, Anita Arasaretnam, Sarkhara Sharma, Frances Aldridge, Bhupinder Sharma, Andrew Wotherspoon, Betty Cheung, Corinne De Lord, Rosalynd Johnston, Shireen Kassam, Ruth Pettengel, Kim Linton, Paul Greaves, Lucy Cook, Kikkeri N. Naresh, Kate Cwynarski, Toby A. Eyre, Ian Chau, David Cunningham, Sunil Iyengar
Journal: Blood Cancer Journal (2023)
Two p53s in a Pod: Co‐occurring plasma cell myeloma and therapy‐related myeloid neoplasm following lenalidomide therapy
Authors: Jorge Monge, Meri Razavi, Liming Bao, Sanjay S. Patel
Journal: American Journal of Hematology (2023)

Jorge Monge receives consulting fees from Bristol Myers Squibb. Meri Razavi, Liming Bao, and Sanjay S. Patel have no conflicts of interest to disclose.
Differential Associations of GAD Antibodies (GADA) and C-Peptide With Insulin Initiation, Glycemic Responses, and Severe Hypoglycemia in Patients Diagnosed With Type 2 Diabetes
Authors: Baoqi Fan, Cadmon K.P. Lim, Emily W.M. Poon, Eric S.H. Lau, Hongjiang Wu, Aimin Yang, Mai Shi, Claudia H.T. Tam, Samuel Y.S. Wong, Eric Kam-Pui Lee, Maggie H.T. Wang, Natural H.S. Chu, Risa Ozaki, Alice P.S. Kong, Elaine Chow, Ronald C.W. Ma, Andrea O.Y. Luk, Juliana C.N. Chan
Journal: Diabetes Care (2023)

OBJECTIVE We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In 5,230 Chinese patients (47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 [interquartile range 1, 12] years), enrolled consecutively in 1996–2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes. RESULTS At baseline, 28.6% (n = 1,494) had low CP (&amp;lt;200 pmol/L) and 4.9% (n = 257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+, and, in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.15–1.84, P = 0.002) for insulin initiation versus the GADA− group, while the low-CP group had an aHR of 0.88 (0.77–1.00, P = 0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (−1.9% at month 6; −1.5% at month 12 vs. −1% in the other three groups). The aHR of severe hypoglycemia was 1.29 (95% CI 1.10–1.52, P = 0.002) in the low-CP group and 1.38 (95% CI 1.04–1.83, P = 0.024) in the GADA+ group. CONCLUSIONS There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.
Etiology, Diagnosis, and Modern Management of Chronic Pancreatitis
Authors: Stephanie M. Cohen, Tara S. Kent
Journal: JAMA Surgery (2023)

Importance The incidence of chronic pancreatitis is 5 to 12 per 100 000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves nutrition optimization, pain management, and when indicated, endoscopic and surgical intervention. Objectives To summarize the most current published evidence on etiology, diagnosis, and management of chronic pancreatitis and its associated complications. Evidence Review A literature search of Web of Science, Embase, Cochrane Library, and PubMed was conducted for publications between January 1, 1997, and July 30, 2022. Excluded from review were the following: case reports, editorials, study protocols, nonsystematic reviews, nonsurgical technical publications, studies pertaining to pharmacokinetics, drug efficacy, pilot studies, historical papers, correspondence, errata, animal and in vitro studies, and publications focused on pancreatic diseases other than chronic pancreatitis. Ultimately, the highest-level evidence publications were chosen for inclusion after analysis by 2 independent reviewers. Findings A total of 75 publications were chosen for review. First-line imaging modalities for diagnosis of chronic pancreatitis included computed tomography and magnetic resonance imaging. More invasive techniques such as endoscopic ultrasonography allowed for tissue analysis, and endoscopic retrograde cholangiopancreatography provided access for dilation, sphincterotomy, and stenting. Nonsurgical options for pain control included behavior modification (smoking cessation, alcohol abstinence), celiac plexus block, splanchnicectomy, nonopioid pain medication, and opioids. Supplemental enzymes should be given to patients with exocrine insufficiency to avoid malnutrition. Surgery was superior to endoscopic interventions for long-term pain control, and early surgery (&amp;amp;lt;3 years from symptom onset) had more superior outcomes than late surgery. Duodenal preserving strategies were preferred unless there was suspicion of cancer. Conclusions and Relevance Results of this systematic review suggest that patients with chronic pancreatitis had high rates of disability. Strategies to improve pain control through behavioral modification, endoscopic measures, and surgery must also accompany management of the sequalae of complications that arise from endocrine and exocrine insufficiency.
Intestinal vitamin D receptor protects against extraintestinal breast cancer tumorigenesis
Authors: Yong-Guo Zhang, Yinglin Xia, Jilei Zhang, Shreya Deb, Shari Garrett, Jun Sun
Journal: Gut Microbes (2023)

The microbiota plays critical roles in regulating the function and health of the intestine and extraintestinal organs. A fundamental question is whether an intestinal-microbiome-breast axis exists during the development of breast cancer. If so, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome, and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in the breast. We examined a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDRΔIEC) mice with dysbiosis. We reported that VDRΔIEC mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that VDR deficiency leads to a bacterial profile shift from normal to susceptible to carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing tumor size and number in the breast. Furthermore, treatment with the beneficial bacterial metabolite butyrate or the probiotic Lactobacillus plantarum reduced breast tumors, enhanced tight junctions, inhibited inflammation, increased butyryl-CoA transferase, and decreased levels of breast Streptococcus bacteria in VDRΔIEC mice. The gut microbiome contributes to the pathogenesis of diseases not only in the intestine but also in the breast. Our study provides insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis lead to a high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions represent a new target in the prevention and treatment of breast cancer.
Local excision as a viable alternative to hysterectomy for early-stage cervical cancer in women of reproductive age: a population-based cohort study
Authors: Ying Chen, Yongqiang Zheng, Yaling Wu, Jun Dai, Xiaoran Zhu, Tong Wu, Weicheng Tang, Shuhao Yang, Jinjin Zhang, Su Zhou, Meng Wu, Chun Zhang, Shixuan Wang
Journal: International Journal of Surgery (2023)

Local excision as the main alternative for fertility-sparing surgery (FSS) has been widely used in patients with early-stage cervical cancer to achieve fertility preservation, but its safety and practicability are still questioned. Therefore, The authors evaluated the current application of local excision in early-stage cervical cancer with this population-based study and compared its efficacy with hysterectomy.Women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I cervical cancer at childbearing age (18-49 years) recorded in the Surveillance, Epidemiology and End Results (SEER) database from 2000 to 2017 were included. Overall survival (OS) and disease-specific survival (DSS) rates were compared between local excision and hysterectomy.A total of 18 519 patients of reproductive age with cervical cancer were included, and 2268 deaths were observed. 17.0% of patients underwent FSS via local excision, and 70.1% underwent hysterectomy. Among patients younger than 39 years, OS and DSS of local excision were comparable to those of hysterectomy, whereas, in patients older than 40 years, OS and DSS of local excision were significantly worse than those of hysterectomy. In addition, OS and DSS of local excision were similar to hysterectomy in patients with stage IA cervical cancer, but OS and DSS were inferior to hysterectomy in patients with stage IB cervical cancer who underwent local excision.For patients without fertility requirements, hysterectomy remains the best therapeutic option. However, for patients under 40 years of age diagnosed with stage IA cervical cancer, FSS via local excision is a viable option that can achieve a well-balanced outcome between tumour control and fertility preservation.
Structural Racism in Psychiatric Research Careers: Eradicating Barriers to a More Diverse Workforce
Authors: Alik S. Widge, Ayana Jordan, Nina V. Kraguljac, Christi R.P. Sullivan, Saydra Wilson, Tami D. Benton, Jonathan E. Alpert, Linda L. Carpenter, John H. Krystal, Charles B. Nemeroff, Kafui Dzirasa
Journal: American Journal of Psychiatry (2023)

Investigators from minoritized backgrounds are underrepresented in psychiatric research. That underrepresentation contributes to disparities in outcomes of access to mental health care. Drawing on lived experience, scholarly qualitative reports, and empirical data, the authors review how the underrepresentation of minoritized researchers arises from interlocking, self-reinforcing effects of structural biases in our research training and funding institutions. Minoritized researchers experience diminished early access to advanced training and opportunities, stereotype threats and microaggressions, isolation due to lack of peers and senior mentors, decreased access to early funding, and unique community and personal financial pressures. These represent structural racism-a system of institutional assumptions and practices that perpetuates race-based disparities, in spite of those institutions' efforts to increase diversity and in contradiction to the values that academic leaders outwardly espouse. The authors further review potential approaches to reversing these structural biases, including undergraduate-focused research experiences, financial support for faculty who lead training/mentoring programs, targeted mentoring through scholarly societies, better use of federal diversity supplement funding, support for scientific reentry, cohort building, diversity efforts targeting senior leadership, and rigorous examination of hiring, compensation, and promotion practices. Several of these approaches have empirically proven best practices and models for dissemination. If implemented alongside outcome measurement, they have the potential to reverse decades of structural bias in psychiatry and psychiatric research.
Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models
Authors: Krisztina Futosi, Tamás Németh, Ádám I. Horváth, Clare L. Abram, Simon Tusnády, Clifford A. Lowell, Zsuzsanna Helyes, Attila Mócsai
Journal: The Journal of Experimental Medicine (2023)

Autoinflammatory diseases include a number of monogenic systemic inflammatory diseases, as well as acquired autoinflammatory diseases such as gout. Here, we show that the myeloid Src-family kinases Hck, Fgr, and Lyn are critical for experimental models of gout, as well as for genetically determined systemic inflammation in the Ptpn6me-v/me-v (motheaten viable) mouse model. The Hck-/-Fgr-/-Lyn-/- mutation abrogated various monosodium urate (MSU) crystal-induced pro-inflammatory responses of neutrophils, and protected mice from the development of gouty arthritis. The Src-family inhibitor dasatinib abrogated MSU crystal-induced responses of human neutrophils and reduced experimental gouty arthritis in mice. The Hck-/-Fgr-/-Lyn-/- mutation also abrogated spontaneous inflammation and prolonged the survival of the Ptpn6me-v/me-v mice. Spontaneous adhesion and superoxide release of Ptpn6me-v/me-v neutrophils were also abolished by the Hck-/-Fgr-/-Lyn-/- mutation. Excessive activation of tyrosine phosphorylation pathways in myeloid cells may characterize a subset of autoinflammatory diseases.
Applying Intersectionality to Better Characterize Healthcare Disparities for Critically Ill Adults
Authors: Gwenyth L. Day, Edward P. Havranek, Eric G. Campbell, Anuj B. Mehta
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Applying Intersectionality to Better Characterize Healthcare Disparities for Critically Ill Adults." American Journal of Respiratory and Critical Care Medicine, 207(12), pp. 1639–1641